How does the ketogenic diet’s upregulation of glutathione play a part in healing your brain from mental illness and neurological disorders?

Glutathione is the brain’s main antioxidant system. The ketogenic diet’s ability to upregulate glutathione production is particularly helpful for people with mental illness or neurological disorders. Ketogenic diets increase the production of glutathione in the brain. Other mechanisms in which glutathione treats mental illness and neurological issues are leaky gut repair, reduction in brain inflammation through improved immune system response of macrophages, enhanced repair of the blood-brain barrier (BBB). Upregulation of glutathione production also improves liver function, which reduces the load of assaults in the body that could later impair brain function (e.g., heavy metals, xenoestrogens).

Introduction

If you have read very much at all on this blog, you have learned about inflammation and oxidative stress, and how those can create symptoms of mental illness and neurological disorders. You may also have read what I have written about the amazing anti-oxidant system you have in your own body that helps combat inflammation and oxidative stress. This endogenous (your body makes it!) antioxidant is glutathione and your production of glutathione is increased when you go on a ketogenic diet.

This post will discuss why the upregulation in glutathione that you get on a ketogenic diet is so important in treating your mental illness or neurological issues. We will specifically talk about why the ketogenic diet’s ability to upregulate glutathione is one of the major ways it helps treat your symptoms.

Other blog posts (coming soon!) will discuss what glutathione is, how it is made in your body, and what you can do to increase your endogenous glutathione production that will supercharge the already healing effects of your ketogenic diet for mental illness.

But first, let’s talk about why you need the upregulated glutathione you get on a ketogenic diet, specifically to treat your mental illness and reduce your symptoms.

Glutathione heals your Leaky Gut.

You may have started your ketogenic diet with digestive issues of varying severity. When they study people with irritable bowel syndrome, they find signs that glutathione is diminished. This is likely because it is being constantly depleted in its efforts to combat oxidative stress in the gut.

Suppose there is not enough glutathione to reduce inflammation and combat oxidative stress. In that case, you get cell damage, which gives you those awful digestive symptoms. As glutathione levels diminish, the gut cannot repair itself, becoming leaky. A leaky gut over activates the immune system in your body, increasing brain immune activity and neuroinflammation.

Neuroinflammation is an underlying factor in the pathology of every mental illness I have written about on this blog thus far. We all know that the health of our gut affects the health of our brain and our mood. 

So while you are on your ketogenic diet and your glutathione is being upregulated, you will keep oxidative stress down in your gut. That is going to help your gut heal (finally) and, in turn, reduce your neuroinflammation and oxidative stress levels in your brain. And that is one of the ways a ketogenic diet will help you treat your mental illness. 

Glutathione and your immune system

close up of an isolated macrophage

People on a ketogenic diet remark that they are much less sick and get illnesses less often. You may be wondering what that is all about. There are a lot of important ways that a ketogenic diet improves immune system function. But specific to how a ketogenic diet increases glutathione and how that improved production of glutathione enhances the immune system, we need to talk about macrophages. Adequate glutathione is required to make white blood cells (macrophages) an important immune system component.

Healthy macrophages in a sufficient number produce a swift and crucial defense in attacking bacteria and viruses. You want a strong, immediate, and crushing immune reaction to invaders. What you don’t want is a long, drawn-out, and ineffective battle that keeps inflammatory cytokines high and continues to create brain inflammation for long periods. 

Glutathione and your blood-brain barrier

Rhea, E. M., & Banks, W. A. (2019). Role of the blood-brain barrier in central nervous system insulin resistance. Frontiers in neuroscience13, 521. https://doi.org/10.3389/fnins.2019.00521

Your blood-brain barrier may very well be leaky if you are suffering from a mental illness or a neurological disorder. And this is a huge problem. You need that blood-brain barrier intact and working well to protect your brain from toxins. Otherwise, molecules that were never supposed to get near your brain do exactly that. This triggers an immune response in your brain to fight off those molecules that should not be there. This immune response in your brain produces inflammatory cytokines. These cytokines produce cellular damage as they attempt to combat the threat. Which would be fine if we did not have a constant barrage of molecules entering the brain that should not be there due to a leaky blood-brain barrier. The chronic neuroinflammation that develops because of nonstop brain immune system activation because of your leaky blood-brain barrier is an underlying cause of your symptoms.  

It just so happens that ketogenic diets enhance the repair and maintenance of the blood-brain barrier in various ways. First, they enhance the creation of nice, tight gap junctions, which is the part of the BBB that becomes leaky. Ketogenic diets also increase energy production in astrocytes, which is one of the primary neuronal bodies responsible for the health of the BBB.  

Thus, the beneficial effects of the ketogenic diet may depend on increased brain uptake of [ketone bodies] KBs to match metabolic demand and repair of a disrupted [blood-brain barrier] BBB.

CellKBs up-regulate cell migration and expression of gap junction proteins Banjara, M., & Janigro, D. (2016). Effects of the ketogenic diet on the blood-brain barrier. Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease; Susan, AM, Ed, 289-304. DOI: 10.1093/med/9780190497996.001.0001

The upregulation in glutathione on a ketogenic diet helps maintain and repair the blood-brain barrier. 

Glutathione and your liver

Cline, J. C. (2015). Nutritional aspects of detoxification in clinical practice. Alternative Therapies in Health & Medicine21(3).

Your liver cannot detox your body from environmental assaults without adequate levels of glutathione. Unchecked environmental assaults, regardless of whether or not they get through your blood-brain barrier, can create neuroinflammation. 

The liver requires glutathione to help detox you from the following inhibitors to your mental health. Each of these deserves a separate post to explain how they contribute to the development of psychiatric disorders. 

  • drug metabolites
  • mycotoxins
  • heavy metals
  • pesticides
  • herbicides
  • xenoestrogens   

You need the upregulation of glutathione that happens on a ketogenic diet to help your body detox from the things that impair your brain health and create your symptoms. 

Glutathione and your brain

Let me be perfectly clear. Glutathione is THE MAIN ANTIOXIDANT that your brain uses to keep itself healthy and functioning. It’s not Vitamin C and it’s not Vitamin E, although those are used as cofactors to make glutathione. If you want a healthy brain, you want as much glutathione as your body wants to produce to protect and repair neurons from damage.

Suppose you have a mental illness or neurological disorder. In that case, you likely have parts of your brain that are particularly low in glutathione. Some of the areas of the brain found to be particularly low in glutathione in specific disorders include the following:

  • Lower posterior cingulate cortex in Obsessive-Compulsive Disorder (OCD)
  • Substantia nigra in Parkinson’s Disease (PD)
  • Occipital and prefrontal cortex in Depression
  • Prefrontal cortex in Bipolar Disorder and Schizophrenia
The brain, vintage engraved illustration.

Increasing glutathione production could help combat oxidative stress in particular parts of the brain relevant to your particular diagnosis. Thereby possibly reducing your symptoms.  

Even if decreased glutathione levels have not been found in particular brain structures for your disorder, there is an overall consensus in the literature that psychiatric and neurological diagnoses have increased levels of oxidative stress and lower glutathione levels in general. 

Glutathione (GSH) is arguably the most important endogenous antioxidant in the brain. In recent years, aberrant GSH levels have been implicated in different psychiatric disorders, including stress-related psychopathologies.

Zalachoras, I., Hollis, F., Ramos-Fernández, E., Trovo, L., Sonnay, S., Geiser, E., Preitner, N., Steiner, P., Sandi, C., & Morató, L. (2020). Therapeutic potential of glutathione-enhancers in stress-related psychopathologies. Neuroscience and biobehavioral reviews114, 134–155. https://doi.org/10.1016/j.neubiorev.2020.03.015

And so, using a ketogenic diet to increase glutathione levels in the brain specifically is one of the mechanisms by which it is a valid potential treatment for your mental illness or neurological disorder. 

Conclusion

There are a lot of benefits for someone struggling with mental illness or neurological symptoms to increased glutathione production. And the ketogenic does exactly that!

Now, you may have some genetic differences that interfere with your ability to make and recycle glutathione. It may be harder for you to make it, and that would be helpful to know. If you want to deep dive into your own body’s ability to make glutathione I would recommend a test through 23andMe (affiliate link). Remember, a portion of your 23andMe can be paid for with your health savings account (HSA) or (FSA) if you have that benefit.

Once you have your 23andMe data you can subscribe to this amazing website Genetic Life Hacks (affiliate link) which will analyze it and report how well your genes support your ability to make and reuse this important endogenous antioxidant your healing brain needs so badly!

No matter what you find out, don’t despair. There are things we can do to increase your glutathione production, even on a ketogenic diet which does such a great job making more of it in the first place.

You need to read this article about thiamine deficiency because a thiamine deficiency can get in the way of your ability to make glutathione. And you may be entering your ketogenic diet thiamine deficient! 

Be sure to get plenty of magnesium, as that activates thiamine, so it can do its thing to help make glutathione.

If you found the above article helpful, you may also like this other blog post talking discussing glutathione.

I am a mental health counselor who practices functional and nutritional psychiatry principles, so feel free to contact me if you would like help on your healing journey. You can learn more about me, and my telehealth and teleconsultation work with clients here.

Like what you are reading on the blog? Want to learn about upcoming webinars, courses, and even offers around support and working with me towards your wellness goals? Sign up!

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